Willingness to vaccinate children against COVID-19 declined during the pandemic.

OBJECTIVES: To document the level of vaccine hesitancy in caregivers' of children younger than 12 years of age over the course of the pandemic in Pediatric Emergency Departments (ED). Study design Ongoing multicenter, cross-sectional survey of caregivers presenting to 19 pediatric EDs in the USA, Canada, Israel, and Switzerland during first months of the pandemic (phase1), when vaccines were approved for adults (phase2) and most recently when vaccines were approved for children (phase3). RESULTS: Willingness to vaccinate rate declined over the study period (59.7%, 56.1% and 52.1% in the three phases). Caregivers who are fully vaccinated, who have higher education, and those worried their child had COVID-19 upon arrival to the ED, were more likely to plan to vaccinate in all three phases. Mothers were less likely to vaccinate early in the pandemic, but this hesitancy attenuated in later phases. Older caregivers were more willing to vaccinate, and caregivers of older children were less likely to vaccinate their children in phase 3. During the last phase, willingness to vaccinate was lowest in those who had a primary care provider but did not rely on their advice for medical decisions (34%). Those with no primary care provider and those who do and rely on their medical advice, had similar rates of willingness to vaccinate (55.1% and 52.1%, respectively). CONCLUSIONS: COVID-19 vaccine hesitancy is widespread and growing over time, and public health measures should further try to leverage identified factors associated with hesitancy in order to enhance vaccination rates among children.

[Male to female sex reassignment surgery with a new surgical simulation device using a human perfused cadaver SIMLIFE®: New paradigm in transsexual surgery education ?] / Aïdoïopoïèse sur modèle cadavérique humain revascularisé pulsatile et ventilé SIMLIFE® : cas isolé ou futur changement de paradigme en chirurgie de réassignation génitale ?

INTRODUCTION: In 2015, we reported our experience with the learning curve in genital reassignment surgery and highlighted a four-step learning concept. CLINICAL CASE: In this article, we present our first vaginoplasty performed on a humanoid model SIMLIFE®, a human body associated with a pulsating circulation device and a ventilation device. RESULTS: The surgical technique included 14 steps. The total surgical time was 182minutes. There was no intraoperative complication, and there was no damage to the urethra or rectum. The intraoperative bleeding measured by the loss of operative fluid was 280mL. We discuss the advantages of this technology perfectly adapted to transsexual surgery. CONCLUSION: We demonstrated the feasibility of vaginoplasty performed on a humanoid model SIMLIFE® and highlighted improvement of the surgical skills with this model. This technology could find many other surgical applications. However, it faces cost constraints and legislation on corpses.

Correction to: Assessing Improvement of Patient Satisfaction Following Facelift Surgery Using the FACE-Q Scales: A Prospective and Multicenter Study.

The Electronic Supplementary Material originally published with this article has been removed due to lack of appropriate permissions from the copyright holder.

Assessing Improvement of Patient Satisfaction Following Facelift Surgery Using the FACE-Q Scales: A Prospective and Multicenter Study.

INTRODUCTION: Assessment of patient satisfaction following an aesthetic surgery has shown an increasing trend over the past years. To date, there is no prospective and comprehensive study evaluating this aspect after surgical facial and neck rejuvenation. The aim of the current work was to address patient satisfaction after face and neck lift surgery using a validated questionnaire. PATIENTS AND METHODS: We present a prospective and multicenter study (five regional centers) involving all patients undergoing face and neck lift surgery between April 2015 and April 2017 in several French centers for aesthetic surgery. All subjects assessed the FACE-Q scales before the procedure, and furtherly at 3-month, 6-month and 12-month follow-ups. RESULTS: Thirty-six patients were included with a median age of 58.5 years old [IQR 54.0-66.0]. The FACE-Q outcomes were significantly higher at 3-month follow-up (p < 0.001). Seventy-five percent of the patients underwent an additional surgical procedure associated with face and neck lift. Particularly, a combined blepharoplasty led to a significant increase in the score of global facial appearance. The patients considered themselves a mean of 6 years younger in the third month after surgery. These results remained constant at six and twelve postoperative months. CONCLUSION: A statistically significant improvement of the FACE-Q scores could be highlighted on every scale, with permanent results at 6 and 12 months postsurgery. We hereby present the first study with evidence that appearance and quality of life outcomes can be reliably assessed after rhytidectomy. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[Development of the facial feminization surgery patient's satisfaction questionnaire (QESFF1): Qualitative phase]. / Élaboration d'un questionnaire de satisfaction encadrant la chirurgie de féminisation faciale chez les patientes transsexuelles male to female (QESFF1) : Phase qualitative.

OBJECTIVE: Facial feminization surgery is becoming a more frequently requested procedure in transsexual male to female patients transformation. A global way of reporting outcomes data and showing the beneficial impact of this specific procedure is necessary. The objective of this study is to develop a reliable and valid tool to report patients' outcomes after facial feminization surgery. METHODS: A systematic literature review, input from experts working with transsexual patients and patient interviews were used to develop the conceptual framework of the questionnaire. It includes the outcomes deemed important to facial feminization surgery and it was used to construct items of the questionnaire. RESULTS: There is no specific tool for measuring patients outcomes after facial feminization surgery. Ten experts and 18 patients participated to this study. The conceptual framework includes the following themes: satisfaction with facial feminine appearance; adverse effects; quality of life. The questionnaire includes fourteen separate Likert scales, with preoperative and postoperative versions. The reliability of the questionnaire is excellent with a medium Alpha score of 0.85. Facial feminization surgery is associated with high patient satisfaction in this sample (83.7±7.41). CONCLUSION: QESFF1 is a reliable questionnaire and its development follows the steps recommended by the patient-reported outcomes process. A large sample pilot test is needed to demonstrate its validity. The QESFF1 can provide physicians with the necessary tools to measure the impact of facial feminization surgery on male to female transsexual patients and also has the potential to support clinical trials.

Multicenter evaluation of quality of life and patient satisfaction after breast reconstruction, a long-term retrospective study.

INTRODUCTION: Breast reconstruction techniques are multiple and they should be chosen in order to improve women's satisfaction and well-being, thus obtaining a personalized treatment. This report's major purpose was to study, through the Breast-Q questionnaire, how the functional and aesthetic outcomes, as well as the complications, of the main autologous breast reconstruction techniques, can affect patients quality of life and well-being at long-term. The secondary purpose was to analyse, thus to identify, the independent factors characterizing the different reconstructive techniques, which may affect patients' satisfaction. METHODS: Women who underwent autologous breast reconstruction through deep inferior epigastric artery perforator or Latissimus dorsi muscle flap from May 2006 to May 2013 were included. The assessment was based on the Breast-Q reconstruction questionnaire. All times of post-mastectomy reconstruction were concerned: immediate, delayed, after previous procedure failure or conversion to another reconstructive technique due to the patient's dissatisfaction. RESULTS: A total of 98 patients were included. Concerning patients satisfaction, the breast-Q score is highest in patients who underwent immediate breast reconstruction, while scores after delayed breast reconstruction, previous surgery failure or conversion to another technique are generally equivalent. Higher scores have been observed in patients who underwent reconstruction through autologous Latissimus dorsi compared to Latissimus dorsi with prosthetic implant reconstruction. CONCLUSION: The authors identified factors of higher patients' satisfaction, like absence of major complication and advanced patient's age, in order to personalize the surgical planning according to the patient's priorities.

Evaluation of donor site morbidity after medial triceps brachii free flap for lower limb reconstruction.

INTRODUCTION: The medial head of the triceps brachii muscle (MTB)-free flap is an attractive solution to cover small-to-medium defects of the lower limb. This muscular head has no well-identified function, suggesting minimal impact of its removal on elbow mobility. The aim of this study was to evaluate the safety and reliability of the harvest procedure and the functional and cosmetic morbidity of this donor site. MATERIALS AND METHODS: Twenty-four consecutive MTB-free flaps were performed for reconstructive surgery of the lower limb between 2011 and 2015. Patients and their records were retrospectively examined. Functional results were evaluated by assessing elbow extension strength using a dynamometer and with a QuickDASH questionnaire. Cosmetic results were assessed using the POSAS observer and patient scales. RESULTS: Twenty-four patients were followed up postoperatively for an average of 33.9 [min 12-max 59] months. No major complication (in particular, no ulnar or radial nerve injury) occurred during harvest. No patient complained of elbow pain or reduction in strength. Elbow extension was complete in all patients and the mean strength was calculated at 89 [61.1-112.5] % of the opposite arm. The POSAS scale scored an average 8.6 [7-21] for the observer and 10 [7-26] for the patient. Cosmetic results using the POSAS scale were satisfactory in all patients. CONCLUSIONS: Objective evaluation of patients who underwent an MTB-free flap for limb reconstruction shows no impact of the harvesting procedure on elbow extension. Patient satisfaction with the donor site was high. From this retrospective study, it appears that this surgery is safe, aesthetically acceptable, and has minimal impact on donor site elbow function.

Maternal pregnancy weight gain and cord blood iron status are associated with eosinophilia in infancy.

OBJECTIVE: Allergic disease is multifactorial in origin. Because iron nutrition affects immune responses and maternal pregnancy weight gain impairs fetal iron delivery while increasing fetal demands for growth, the study examined maternal pregnancy weight gain, newborn iron status and an index of atopic disease, infant eosinophilia. STUDY DESIGN: Within a larger prospective study of healthy newborns at risk for developing iron deficiency anemia, umbilical cord iron indicators were compared to infant eosinophil counts. RESULT: Infants who developed eosinophilia exhibited higher cord reticulocyte-enriched zinc protoporphyrin/heme ratio, P<0.05 and fewer cord ferritin values in the highest (best) quartile, P<0.05. If cord ferritin was in the upper three quartiles, the negative predictive value for infant eosinophilia was 90%. High maternal pregnancy weight gain predicted infant eosinophil counts, P<0.04, and contributed to cord ferritin predicting eosinophilia, P<0.003. CONCLUSION: Poor fetal iron status may be an additional risk factor for infant eosinophilia.

[Aortodigestive fistula and septic wound of the lower leg. A case report]. / Fistule aortodigestive et plaie septique de membre inférieur. À propos d'un cas.

An aortodigestive fistula can be revealed by a peripheral septic wound when patient have aortic endovascular prosthesis. Our clinical case is about a 69-year-old patient with an abscess of the lateral aspect of his left lower limb. He has been treated few years ago for an aorto-abdominal anevrysm by an aortobifemoral prosthesis. In spite of a negative initial assessment for an aortodigestive fistula, anaerobic germs were found into the abscess. The initial treatment associated debridement, negative pressure therapy, dermal substitute and a split thickness skin graft for the loss of cutaneous substance. Months later, in front of an unexplained skin healing delay and fever, we realised new assessment bringing to light an aortodigestive fistula. Furthermore, the local bacterial samples from the wound and the hemocultures found both a lot of Escherichia Coli. The change of the aorto-bifemoral prosthesis and the cure of the aortodigestive fistula allowed the complete healing of the loss of cutaneous substance of the leg. The aortodigestive fistulas have a very high mortality. Because of their difficult diagnosis, their clinical suspicion has to start a complete medical assessment. Every septic wound when patients have vascular prosthesis is suggestive of an aortodigestive fistula.

Time-dependent changes in the brain arachidonic acid cascade during cuprizone-induced demyelination and remyelination.

Phospholipases A(2) (PLA(2)) are the enzymatic keys for the activation of the arachidonic acid (AA) cascade and the subsequent synthesis of pro-inflammatory prostanoids (prostaglandins and tromboxanes). Prostanoids play critical roles in the initiation and modulation of inflammation and their levels have been reported increased in several neurological and neurodegenerative disorders, including multiple sclerosis (MS). Here, we aimed to determine whether brain expression PLA(2) enzymes and the terminal prostagland in levels are changed during cuprizone-induced demyelination and in the subsequent remyelination phase. Mice were given the neurotoxicant cuprizone through the diet for six weeks to induce brain demyelination. Then, cuprizone was withdrawn and mice were returned to a normal diet for 6 weeks to allow spontaneous remyelination. We found that after 4-6 weeks of cuprizone, sPLA(2)(V) and cPLA(2), but not iPLA(2)(VI), gene expression was upregulated in the cortex, concomitant with an increase in the expression of astrocyte and microglia markers. Cyclooxygenase (COX)-2 gene expression was consistently upregulated during all the demyelination period, whereas COX-1 sporadically increased only at week 5 of cuprizone exposure. However, we found that at the protein level only sPLA(2)(V) and COX-1 were elevated during demyelination, with COX-1 selectively expressed by activated and infiltrated microglia/macrophages and astrocytes. Levels of PGE(2), PGD(2), PGI(2) and TXB(2) were also increased during demyelination. During remyelination, none of the PLA(2) isoforms was significantly changed, whereas COX-1 and -2 were sporadically upregulated only at the gene expression level. PGE(2), PGI(2) and PGD(2) levels returned to normal, whereas TXB(2) was still upregulated after 3 weeks of cuprizone withdrawal. Our study characterizes for the first time time-dependent changes in the AA metabolic pathway during cuprizone-induced demyelination and the subsequent remyelination and suggests that sPLA(2)(V) is the major isoform contributing to AA release.

Management of severe hand wounds with Integra® dermal regeneration template.

We report our experience with the use of Integra® for the management of severe traumatic wounds of the hand. Fifteen patients were treated with follow-up ranging from 10 to 37 months. Wounds were associated with an osseous and/or joint and/or tendon exposure. Following Integra® placement, patients were managed with dressings and subsequent split-thickness skin grafting an average of 26 days later. Integra® was successful in achieving durable, functional and aesthetic definitive coverage in 13 of 15 applications while allowing a satisfying pollicidigital prehension. Regarding our clinical experience, Integra® is an effective technique to deal with severe wounds of the hand with exposed tendon and/or bone and/or joint, even in the absence of paratenon or periosteum. This can potentially lessen the need for local rotational or free flap coverage and should be taken into consideration as a viable alternative in traumatic reconstruction of the hand.

CtBP/BARS induces fission of Golgi membranes by acylating lysophosphatidic acid.

Membrane fission is essential in intracellular transport. Acyl-coenzyme As (acyl-CoAs) are important in lipid remodelling and are required for fission of COPI-coated vesicles. Here we show that CtBP/BARS, a protein that functions in the dynamics of Golgi tubules, is an essential component of the fission machinery operating at Golgi tubular networks, including Golgi compartments involved in protein transport and sorting. CtBP/BARS-induced fission was preceded by the formation of constricted sites in Golgi tubules, whose extreme curvature is likely to involve local changes in the membrane lipid composition. We find that CtBP/BARS uses acyl-CoA to selectively catalyse the acylation of lysophosphatidic acid to phosphatidic acid both in pure lipidic systems and in Golgi membranes, and that this reaction is essential for fission. Our results indicate a key role for lipid metabolic pathways in membrane fission.

Role of brefeldin A-dependent ADP-ribosylation in the control of intracellular membrane transport.

The fungal toxin brefeldin A (BFA) dissociates coat proteins from Golgi membranes, causes the rapid disassembly of the Golgi complex and potently stimulates the ADP-ribosylation of two cytosolic proteins of 38 and 50 kDa. These proteins have been identified as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and a novel guanine nucleotide binding protein (BARS-50), respectively. The role of ADP-ribosylation in mediating the effects of BFA on the structure and function of the Golgi complex was analyzed by several approaches including the use of selective pharmacological blockers of the reaction and the use of ADP-ribosylated cytosol and/or enriched preparations of the BFA-induced ADP-ribosylation substrates, GAPDH and BARS-50. A series of blockers of the BFA-dependent ADP-ribosylation reaction identified in our laboratory inhibited the effects of BFA on Golgi morphology and, with similar potency, the ADP-ribosylation of BARS-50 and GAPDH. In permeabilized RBL cells, the BFA-dependent disassembly of the Golgi complex required NAD+ and cytosol. Cytosol that had been previously ADP-ribosylated (namely, it contained ADP-ribosylated GAPDH and BARS-50), was instead sufficient to sustain the Golgi disassembly induced by BFA. Taken together, these results indicate that an ADP-ribosylation reaction is part of the mechanism of action of BFA and it might intervene in the control of the structure and function of the Golgi complex.

Characterization of chemical inhibitors of brefeldin A-activated mono-ADP-ribosylation.

Brefeldin A, a toxin inhibitor of vesicular traffic, induces the selective mono-ADP-ribosylation of two cytosolic proteins, glyceraldehyde-3-phosphate dehydrogenase and the novel GTP-binding protein BARS-50. Here, we have used a new quantitative assay for the characterization of this reaction and the development of specific pharmacological inhibitors. Mono-ADP-ribosylation is activated by brefeldin A with an EC50 of 17.0 +/- 3.1 microg/ml, but not by biologically inactive analogs including a brefeldin A stereoisomer. Brefeldin A acts by increasing the Vmax of the reaction, whereas it does not influence the Km of the enzyme for NAD+ (154 +/- 13 microM). The enzyme is an integral membrane protein present in most tissues and is modulated by Zn2+, Cu2+, ATP (but not by other nucleotides), pH, temperature, and ionic strength. To identify inhibitors of the reaction, a large number of drugs previously tested as blockers of bacterial ADP-ribosyltransferases were screened. Two classes of molecules, one belonging to the coumarin group (dicumarol, coumermycin A1, and novobiocin) and the other to the quinone group (ilimaquinone, benzoquinone, and naphthoquinone), rather potently and specifically inhibited brefeldin A-dependent mono-ADP-ribosylation. When tested in living cells, these molecules antagonized the tubular reticular redistribution of the Golgi complex caused by brefeldin A at concentrations similar to those active in the mono-ADP-ribosylation assay in vitro, suggesting a role for mono-ADP-ribosylation in the cellular actions of brefeldin A.

Possible role of BARS-50, a substrate of brefeldin A-dependent mono-ADP-ribosylation, in intracellular transport.

Brefeldin A (BFA), a fungal metabolite that inhibits membrane transport, potently stimulates an endogenous ADP-ribosylation reaction that selectively modifies two cytosolic proteins of 38 and 50 kDa on an amino acid residue different from those used by all known mADPRTs. The 38-kDa substrate was identified as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), whereas the 50-kDa substrate (BARS-50) was characterized as a novel guanine nucleotide binding protein. Thus, BARS-50 is able to bind GTP and its ADP-ribosylation is inhibited by the beta gamma subunit of GTP-binding (G) proteins. Moreover, BARS-50 was demonstrated to be a group of closely related proteins that appear to be different from all the known G proteins. A partially purified BARS-50 was obtained from rat brain cytosol, which was then used for microsequencing and in functional studies. A similar procedure led to the purification of native (non-ADP-ribosylated) BARS-50. The possible role of the BFA-dependent ADP-ribosylation and of BARS-50 in the maintenance of Golgi structure and function was addressed by examining which of the effects of BFA may be modified by inhibiting this reaction. We find that the BFA-dependent transformation of the Golgi stacks into a tubular reticular network is prevented when the BFA-dependent ADP-ribosylation activity was blocked by specific inhibitors thus indicating that BFA-dependent ADP-ribosylation of cytosolic proteins participate in the dynamic regulation of intracellular transport.

Brefeldin A-induced ADP-ribosylation in the structure and function of the Golgi complex.

Brefeldin A (BFA) is a fungal metabolite that exerts generally inhibitory actions on membrane transport and induces the disappearance of the Golgi complex. Previously we have shown that BFA stimulates the ADP-ribosylation of two cytosolic proteins of 38 and 50 KD. The BFA-binding components mediating the BFA-sensitive ADP-ribosylation (BAR) and the effect of BFA on ARF binding to Golgi membranes have similar specificities and affinities for BFA and its analogues, suggesting that BAR may have a role in the cellular effects of BFA. To investigate this we used the approach to impair BAR activity by the use of BAR inhibitors. A series of BAR inhibitors was developed and their effects were studied in RBL cells treated with BFA. In addition to the common ADP-ribosylation inhibitors (nicotinamide and aminobenzamide), compounds belonging to the cumarin (novobiocin, cumermycin, dicumarol) class were active BAR inhibitors. All BAR inhibitors were able to prevent the BFA-induced redistribution of a Golgi marker (Helix pomatia lectin) into the endoplasmic reticulum, as assessed in immunofluorescence experiments. At the ultrastructural level, BAR inhibitors prevented the tubular-vesicular transformation of the Golgi complex caused by BFA. The potencies of these compounds in preventing the BFA effects on the Golgi complex were similar to those at which they inhibited BAR. Altogether these data support the hypothesis that BAR mediates at least some of the effects of BFA on the Golgi structure and function.

Characterization of the endogenous mono-ADP-ribosylation stimulated by brefeldin A.

We have recently described a novel enzymatic mono-ADP-ribosyl transfer reaction induced by brefeldin A, a well characterized inhibitor of vesicular traffic, which selectively modifies two cytosolic proteins of 38 kDa (p38) and 50 kDa (BARS-50). p38 was identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme and a multifunctional protein involved in several cellular processes; BARS-50 might be a novel G protein, since it is able to bind GTP and the beta gamma subunit of G proteins. We have characterized this enzymatic activity and screened in vitro the effects of different drugs belonging to the coumarine (dicumarol, coumermicin A1 and novobiocin) and quinone (ilimaquinones, benzoquinones and naphtoquinones) class. These drugs blocked the BFA-dependent mono-ADP-ribosylation, showed remarkable effects on Golgi morphology in control cells, and antagonized the tubular reticular redistribution of the Golgi complex in brefeldin A treated cells (see papers of Corda and Colanzi in this issue) suggesting a possible role for ADP-ribosylation in both the cellular effects of brefeldin A and the maintenance of the structure/function of the Golgi complex.

Role of NAD+ and ADP-ribosylation in the maintenance of the Golgi structure.

We have investigated the role of the ADP- ribosylation induced by brefeldin A (BFA) in the mechanisms controlling the architecture of the Golgi complex. BFA causes the rapid disassembly of this organelle into a network of tubules, prevents the association of coatomer and other proteins to Golgi membranes, and stimulates the ADP-ribosylation of two cytosolic proteins of 38 and 50 kD (GAPDH and BARS-50; De Matteis, M.A., M. DiGirolamo, A. Colanzi, M. Pallas, G. Di Tullio, L.J. McDonald, J. Moss, G. Santini, S. Bannykh, D. Corda, and A. Luini. 1994. Proc. Natl. Acad. Sci. USA. 91:1114-1118; Di Girolamo, M., M.G. Silletta, M.A. De Matteis, A. Braca, A. Colanzi, D. Pawlak, M.M. Rasenick, A. Luini, and D. Corda. 1995. Proc. Natl. Acad. Sci. USA. 92:7065-7069). To study the role of ADP-ribosylation, this reaction was inhibited by depletion of NAD+ (the ADP-ribose donor) or by using selective pharmacological blockers in permeabilized cells. In NAD+-depleted cells and in the presence of dialized cytosol, BFA detached coat proteins from Golgi membranes with normal potency but failed to alter the organelle's structure. Readdition of NAD+ triggered Golgi disassembly by BFA. This effect of NAD+ was mimicked by the use of pre-ADP- ribosylated cytosol. The further addition of extracts enriched in native BARS-50 abolished the ability of ADP-ribosylated cytosol to support the effect of BFA. Pharmacological blockers of the BFA-dependent ADP-ribosylation (Weigert, R., A. Colanzi, A. Mironov, R. Buccione, C. Cericola, M.G. Sciulli, G. Santini, S. Flati, A. Fusella, J. Donaldson, M. DiGirolamo, D. Corda, M.A. De Matteis, and A. Luini. 1997. J. Biol. Chem. 272:14200-14207) prevented Golgi disassembly by BFA in permeabilized cells. These inhibitors became inactive in the presence of pre-ADP-ribosylated cytosol, and their activity was rescued by supplementing the cytosol with a native BARS-50-enriched fraction. These results indicate that ADP-ribosylation plays a role in the Golgi disassembling activity of BFA, and suggest that the ADP-ribosylated substrates are components of the machinery controlling the structure of the Golgi apparatus.